Ecole Normale Supérieure de Lyon - CNRS - Université de Lyon Claude Bernard, Molecular Biology of the Cell Laboratory/UMR5239, 46, Allée d'Italie, 69364, Lyon Cedex 07, France.
Aging Cell. 2010 Dec;9(6):991-1003. doi: 10.1111/j.1474-9726.2010.00625.x. Epub 2010 Oct 29.
Oxidatively damaged proteins accumulate with age in many species (Stadtman (1992) Science257, 1220-1224). This means that damage must be reset at the time of reproduction. To visualize this resetting in the roundworm Caenorhabditis elegans, a novel immunofluorescence technique that allows the detection of carbonylated proteins in situ was developed. The application of this technique revealed that carbonylated proteins are eliminated during C. elegans reproduction. This purging occurs abruptly within the germline at the time of oocyte maturation. Surprisingly, the germline was markedly more oxidized than the surrounding somatic tissues. Because distinct mechanisms have been proposed to explain damage elimination in yeast and mice (Aguilaniu et al. (2003) Science299, 1751-1753; Hernebring et al. (2006) Proc Natl Acad Sci USA103, 7700-7705), possible common mechanisms between worms and one of these systems were tested. The results show that, unlike in yeast (Aguilaniu et al. (2003) Science299, 1751-1753; Erjavec et al. (2008) Proc Natl Acad Sci USA105, 18764-18769), the elimination of carbonylated proteins in worms does not require the presence of the longevity-ensuring gene, SIR-2.1. However, similar to findings in mice (Hernebring et al. (2006) Proc Natl Acad Sci USA103, 7700-7705), proteasome activity in the germline is required for the resetting of carbonylated proteins during reproduction in C. elegans. Thus, oxidatively damaged proteins are eliminated during reproduction in worms through the proteasome. This finding suggests that the resetting of damaged proteins during reproduction is conserved, therefore validating the use of C. elegans as a model to study the molecular basis of damage elimination.
在许多物种中,随着年龄的增长,氧化损伤的蛋白质会积累(Stadtman(1992)Science257,1220-1224)。这意味着在繁殖时必须重置损伤。为了在秀丽隐杆线虫中可视化这种重置,开发了一种新的免疫荧光技术,该技术允许原位检测羰基化蛋白质。该技术的应用表明,在秀丽隐杆线虫的繁殖过程中,羰基化蛋白质被消除。这种清除在卵母细胞成熟时突然发生在生殖系中。令人惊讶的是,生殖系比周围的体细胞组织明显更氧化。因为已经提出了不同的机制来解释酵母和小鼠中的损伤消除(Aguilaniu 等人(2003)Science299,1751-1753;Hernebring 等人(2006)Proc Natl Acad Sci USA103,7700-7705),因此测试了线虫和其中一种系统之间可能存在的共同机制。结果表明,与酵母不同(Aguilaniu 等人(2003)Science299,1751-1753;Erjavec 等人(2008)Proc Natl Acad Sci USA105,18764-18769),在线虫中,羰基化蛋白质的消除不需要确保长寿的基因 SIR-2.1 的存在。然而,与在小鼠中发现的相似(Hernebring 等人(2006)Proc Natl Acad Sci USA103,7700-7705),在线虫生殖系中,蛋白酶体活性对于繁殖过程中羰基化蛋白质的重置是必需的。因此,在线虫繁殖过程中,氧化损伤的蛋白质通过蛋白酶体被消除。这一发现表明,在繁殖过程中重置受损蛋白质是保守的,因此验证了使用秀丽隐杆线虫作为研究损伤消除分子基础的模型的有效性。